Human unrestricted somatic stem cells ameliorate sepsis‐related acute lung injury in mice

Abstract

Background Aims Sepsis and related disorders, especially acute lung injury (ALI), are the most challenging life‐threatening diseases in the hospital intensive care unit. Complex pathophysiology, unbalanced immune condition, and high rate of mortality complicate the treatment of sepsis. Recently, cell therapy has been introduced as a promising option to recover the sepsis symptoms. The aim of this study was to investigate the therapeutic potential of human unrestricted somatic stem cells (USSCs) isolated from human umbilical cord blood in the mouse model of ALI. USSCs significantly enhanced the survival rate of mice suffering from ALI and suppressed concentrations of proinflammatory mediators TNF‐α, and interleukin (IL)‐6, and the level of anti‐inflammatory cytokine IL‐10. ALI mice injected by USSCs showed notable reduction in lung and liver injury, pulmonary edema, and hepatic enzymes, compared with the control group. These results determined the in vivo immunomodulatory effect of USSCs for recovery of immune balance and reduction of tissue injury in the mouse model of ALI. Therefore, USSCs can be a suitable therapeutic approach to manage sepsis disease through the anti‐inflammatory potential.

Mesenchymal stem cell and endothelial progenitor cells coinjection improves LPS‐induced lung injury via Tie2 activation and downregulation of the TLR4/MyD88 pathway

“…TNF‐α, IL1‐β, and IL‐6 are the most released inflammatory cytokines during sepsis 46 . Stem cell therapy has been shown to balance the released inflammatory cytokines through the anti‐inflammatory potential 11 . In this study, we have observed that the signaling pathways associated with TLR4 are activated in mice with LPS induction, and as a result, the MyD88, which is the downstream pathway of TLR4, is also activated.…”

“…In recent years, many preclinical studies have reported the anti‐inflammatory effects of stem cells on different species of animals with sepsis 24–26 . Some types of stem cells, including MSCs and umbilical cord blood stem cells have been used as a new treatment option in clinical trials of sepsis 11,25,27 …”

“…Easy access, noninvasiveness, the ability of proliferative and migratory of the transplanted cells are the main features that must be considered to achieve the desired results. In addition, to reduce the side effects of sepsis, increasing inflammatory responses, reduction of organ damage, and mortality are desired 11 . MSCs derived from various sources have been frequently introduced as a candidate for cell therapy in animal models of sepsis 28,29 due to their significant effects on immune modulation and regeneration.…”

“…So, there is an urgent need for new alternative therapies. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been recently demonstrated 11–14 . In coculture systems, MSCs have been found to be involved in the hematopoietic process by secreting some types of cytokines, which could determine the fate of hematopoietic stem cells 15 .…”

“…The immunomodulatory properties of mesenchymal stem cells (MSCs) have been recently demonstrated. [11][12][13][14] In coculture systems, MSCs have been found to be involved in the hematopoietic process by secreting some types of cytokines, which could determine the fate of hematopoietic stem cells. 15 These cells have been shown to reduce inflammation in some diseases such as type 2 diabetes, rheumatoid arthritis, and sepsis.…”